Certain cell membrane proteins are responsible for the selective permeability of the cell to small molecules. Of particular interest are the systems responsible for the transport of specfic sugars to be metabolized by the cell, and the membrane proteins that produce and regulate the electrical activity in nerve cells by acting as gates and pumps for specific ions. Prerequisites for the detailed understanding of the molecular mechanisms of these transport proteins are their isolation and reconstitution into artificial membranes in biologically active form (80). We have developed a novel approach ("transport specificity fractiontion") for the identification and purification of such transport proteins; this technique uses reconstitution of the protein of interest into artificial lipid vesicles as a physical tool for its purification. We have successfully employed this strategy to identify and purify the sugar transport system from human red blood cells. We subsequently used this powerful new tool to purify 100-fold of Ca ions transport system from nerve terminals; no comparable degree of purification of any ion transport from the central nervous system has yet been demonstrated. We are currently investigating the precise role of this protein in the regulation of neurotransmitter release, and its possible regulation by the opiates. In parallel, we are employing "transport specificity fractionation" to purify the Na ion gate from myelinated axons in mammalian brain.